Is Chronic Fatigue Syndrome (ME/CFS) an Autoimmune Disorder?

November 6, 2011

Posted by Cort Johnson

Could chronic fatigue syndrome be an autoimmune disorder? The Fluge/Mella Rituximab study was effective in at least temporarily reducing the symptoms of about 60% of the chronic fatigue syndrome patients in the study – a fact that no doubt shocked many who considered CFS purely a neuropsychiatric disorder.

Rituximab started out as a chemotherapy drug but is now being used effectively in a variety of autoimmune disorders and is being studied in even more. Could Rituximab’s success mean that a large portion of the ME/CFS community actually suffers from an autoimmune disorder?The Fluge/Mella team suggested so, stating their results indicated

“CFS may be an autoimmune disease, often preceded by an infection, and targeting specific parts of the nervous system”

Autoimmune Disorders and Chronic Fatigue Syndrome: A Short Review

An autoimmune disorder occurs when the immune system mistakes human cells for intruders and begins attacking them. If ME/CFS (or parts of it) is an autoimmune disorder it’s not alone; in 2001 the NIH reported that approximately 5% of the US population is believed to have one. Virtually every organ and tissue in the body can end up being attacked by the body and over 80 autoimmune disorders have been identified.

Until the Rituximab studies came out research into the autoimmune aspects of ME/CFS was scanty evidence ME/CFS was low. A few studies found auto-antibodies (antibodies that attack human cells) in ME/CFS patients but the results varied and a followup study failed to confirm the positive results that did pop up.

That was before, though, and now more intensive research will surely follow. The CFIDS Association of America, in fact, had a grant proposal to do a comprehensive study of autoimmune issues under review as the Rituximab story broke.

Now that the autoimmune issue has been starkly raised by the Rituximab study we take a look at some indirect evidence for CFS as an autoimmune disorder ; if you were to take away the labels and the history and just compared some fundamental aspects of CFS and auto-immune disorders – would you be inclined to fit ME/CFS into the autoimmune disorder category?

It turns out that the answer is perhaps yes. ME/CFS shares at least nine factors with the other auto-immune disorders. They include a gender imbalance tilted towards women, improved symptoms during pregnancy, a strong stress response connection, a high degree of genetic susceptibility, common pathogen triggers, Th2 dominance, high levels of oxidative stress, involvement of the innate immune system, and now symptom improvement using an immune suppressant (Rituximab).

Gender

“It is well established that gender plays a profound role in the incidence of autoimmunity”Anatoly Rubotskov in ‘Genetic and Hormonal Factors in female-based auto-immunity’

With ME/CFS and autoimmune disorders displaying the same gender imbalance (@75% of those afflicted are women) gender is one of the more intriguing commonalities. Female gender imbalance in illness is not common; outside of gynecological and reproductive disorders it occurs in osteoporosis, depression, anxiety, arthritis, ME/CFS, Fibromyalgia, irritable bowel syndrome, TMJ, Alzheimer’s, and many autoimmune disorders.http://www.phrma.org/research/facts-about-diseasesconditions-affecting-women-united-states.

Why women are more prone to develop autoimmune disorders is not clear but researchers think it probably have to do with two factors; an increased inflammatory response and the involvement of sex hormone, both of which are subjects of interest in ME/CFS. (Interestingly, men with autoimmune disorders often have more severe forms of them.)

Women tend to have more active immune responses than men with higher levels of circulating antibodies, T helper cells and a stronger cytokine response to infections. In general women have a stronger Th1 response, except during pregnancy when they shift to a Th2 pattern. (Researchers, in fact, prefer to use female laboratory animals in their studies because their immune response is so much stronger). The stronger immune response in women would seem to place them more at risk of developing an over-active immune response; ie an auto-immune disorder.

The strong influence female sex hormones have on the immune system provides an interesting feedback loop as the female sex hormone estrogen stimulates B-cell development and auto-antibody production. Progesterone, which is low in some women with ME/CFS, on the other hand, is an immune suppressant. Sex hormones may also play a role in a pattern of altered symptoms during pregnancy that is often seen in ME/CFS and some autoimmune disorders (see below).

Improved symptoms during pregnancy

Symptom improvement during pregnancy in both CFS and several autoimmune disorders suggests that sex hormones may play a role in both. (Symptoms may also improve in auto-immune disorders during parts of the menstrual cycle and/or when using oral contraceptives. Not all autoimmune disorders display this pattern.) Symptom improvement is generally highest during the third trimester when estrogen and progesterone levels are the highest. As noted above, sex hormones such as estrogen have a strong regulatory effects on the immune system and have been shown to increase both normal antibody and autoantibody levels.

The tendency of women with ME/CFS to feel substantially better during part of their pregnancy is well-known . The Staines/Peterson group working out of Bond University in Australia presented preliminary findings at the IACFS/ME conference in Ottawa in 2011 suggesting that genes involved in pregnancy were being expressed differently in women with ME/CFS. A CDC study by Boneva presented at the same conference suggested startlingly high rates of gynecological abnormalities that may be tied to hormonal imbalances were present in women with CFS.

The tendency of middle aged women to get CFS is intriguing given the fact that being pregnant appears to increase the risk of getting an autoimmune disorder (and ME/CFS?). Given the much lower rate of children with ME/CFS than adolescents and adults one has to wonder if hormonal issues beginning in adolescence play a role. The fact that estrogen levels do not appear to be altered in women with auto-immune disorders, however, suggests that the issue is complicated (tissue receptivity to estrogen is another issue) and that other factors probably also play a role in the gender imbalance.

Interestingly, given how common testosterone treatment for ME/CFS is in some clinics, males with rheumatoid arthritis tend to have lower testosterone levels.

Genetic Susceptibility

“To a large extent , predisposition to auto-immune disease is genetically inherited”Anatoly Rubotskov in ‘Genetic and Hormonal Factors in female-based auto-immunity’

Several studies have suggested that genetics plays an unusually strong role in autoimmune disorders and an even stronger role in both fibromyalgia and chronic fatigue syndrome. At the recent IACFS/ME conference in Ottawa Dr. Clauw stated that aside from single gene mutation disorders that genetics may play a stronger role in FM than any other disorder. A recent paper by the Lights suggested that ME/CFS may have a similarly strong genetic component. This is intriguing given the theory that autoimmune disorders in women may be largely driven by genetic alterations in their X chromosomes. Could a similar process be occurring in FM and CFS?

The Stress-Autoimmune Response

Of course, stress alone does not cause autoimmune diseases…and removing stress alone does not cure (them). But relaxation can help one’s body to heal and to respond to the advanced medications that have been developed in recent years to treat such diseases. The treatment of autoimmune disease should …include stress management and behavioral intervention to prevent stress-related immune imbalance.Esther Sternberg, MD. “The stress response and autoimmune disease–what have we learned? “

High levels of stress, including infection (see below) and psychological distress, have been shown to commonly precede the development of autoimmune disorders. According to one review many retrospective studies found that a high proportion (up to 80%) of autoimmune disorder patients reported uncommon emotional stress prior to onset suggesting that stress related hormones may play a role in the development of these disorders.

Given the tight interaction between the stress response and immune systems, with both axes of the stress response being important immune regulators, it’s no surprise that the neuroendocrine system is a major area of research in autoimmune conditions (as it has been in ME/CFS) and that behavioral interventions to reduce stress are used in both types of disorders to reduce symptoms. (Both axes of the stress, the HPA axis and the sympathetic nervous system, appear to be perturbed in ME/CFS.)

Pathogens

It is clear that, in many cases, an infection is necessary for the development of overt (autoimmune) diseaseDe Logu “Infectious Diseases and Auto-immunity”

Pathogens and infections are, of course, major stressors and infectious triggers have long been associated with both auto-immune diseases and CFS. Auto-immune elements are part of our makeup – but how they go from being an innocuous part of it to ravaging it – is a central question. Animal studies have shown many times that often it’s an infection that tips the tables. Unfortunately, for researchers, often times an auto-immune process often proceeds for some time before it becomes apparent; thus, just as in CFS, an infection may indeed have tipped the balance but identifying what pathogen was responsible was responsible can be difficult.

One theory suggests that pathogens that produce ‘super-antigens’, which can activate B-lymphocytes en masse – essentially overloading and confusing them into attacking human tissues – can trigger an auto-immune response. Here too we have a CFS tie-in; Dr. Huber is investigating whether HERV’s trigger a super-antigen response in people with ME/CFS.

Epstein Barr Virus (EBV) and Molecular Mimicry

Viral and bacterial infections are the main candidate environmental factors due to their capacity to elicit strong immune activation and to induce autoimmune diseases in animal models, as well as the correlation of several pathogens with autoimmune diseases in humans.

De Logu “Infectious Diseases and Auto-immunity”

The best guess for a pathogen triggered autoimmune condition is EBV. No pathogen has been more closely tied to CFS, and EBV, which maintains its latency in the B-cells Rituximab attacks, has been linked to a number of auto-immune disorders. The high viral loads seen in infectious mononucleosis are associated with an increased risk of getting CFS or multiple sclerosis may be able to activate T cells that attack human tissues. Peterson believes that something called molecular mimicry could be playing a role in whatever autoimmune processes are occurring in ME/CFS.

Molecular mimicry occurs when molecules from another organism are so alike to those found in the host that the immune system mounts an attack against both. Dr. Peterson cited a fairly common condition called autoimmune thyroiditis he sees in the patient population that could be caused by molecular mimicry involving EBV.

Others – Other pathogens are associated with other autoimmune disorders. Klebsiella pneumoniae and coxsackievirus B (an enterovirus) have been strongly correlated with ankylosing spondylitis and diabetes mellitus type 1.
< =h2>Oxidative Stress High antibody levels can produce increased rates of oxidative stress and high rates of oxidative stress an may also be able to trigger an autoimmune reaction. This could occur when oxidative stress (free radicals) deforms molecules and proteins enough to trigger the immune system – which recognizes them as something damaged ; ie – not-self, to attack both them and human tissues that resemble them.

A recent study found auto-antibodies against a protein involved in the transport of glutathione byproducts in several autoimmune disorders. Because glutathione is a key anti-oxidant, the inability to remove its free radical b- products could cause more free radical damage increased oxidative stress, which, of course, is high in CFS.

Some researchers believe that some autoimmune disorders currently believed to be B-cell antibody disorders are actually auto-immune responses to high levels of oxidative stress.Maes has found evidence that this may be occurring in ME/CFS. He has found autoimmune by-products of oxidative stress in both ME/CFS and depression. If Maes is right at least part of the autoimmune process in ME/CFS could be reduced by reducing levels of oxidative stress. Maes reported that he has found strong evidence of autoimmune process in about 30% of ME/CFS patients and more data from him will be upcoming.‘

Auto-immunity’ Redefined-- The paradigm of B and T cell mediated autoimmune problems that has been pervasive in the medical profession for the past 50 years has been taking its knocks of late. The problem is how to account for chronic inflammatory conditions that appear to be caused by immune injury of the body’s tissues (auto-immunity) but which do not display the characteristic auto-antibodies and other problems found in classical autoimmune disorders.

“We have every reason to believe that therapies that selectively modulate the functioning of the innate system will prove just as valuable as treatments that intervene with the adaptive immune system.”

At the IACFS/ME Conference in Ottawa, Dr. Montoya called for more focus on the ‘early’ or innate immune response in CFS. Interestingly, it’s become clear that many chronic inflammatory and autoimmune disorders don’t display the classic T and B cell responses that immunologists have concentrated on for so long – that something else is going on – and that something else probably involves the innate immune system.

The innate (or early) immune system is characterized by a rapid immune response involving natural killer cell activity, phagocytosis, toll-like receptor activation, the complement system and the production of cytokines, chemokines, nitric oxide and others. Interferon’s, tumor necrosis alpha and some interleukins including IL-10 appear to be the main drivers of innate immune system driven auto-immunity. (Interestingly interferon administration causes symptoms remarkably similar to those found in ME/CFS).

Innate immune system processes are incredibly complex but some things stand out; at least three regulators of the innate immune system; IL-10, TGF-B and adenosine ( a part of the purinergic system), have been highlighted in CFS. A preliminary study by the Staines/Peterson group suggests that the purinergic system may indeed be off kilter. Interestingly, adenosine is often formed in areas with low blood oxygen levels (hypoxia, ischemia) – which, given the low blood volume present in ME/CFS – may be present in CFS and adenosine potentiates IL-10 production, which is usually high in ME/CFS.

The idea that the innate immune system may play in auto-immunity has lead to a revaluation of what autoimmune disorders are and a proposal that a spectrum of autoimmune disorders exists with those driven by classic B-cell responses on one side and one driven by the innate immune system on the other. Where ME/CFS would fall is, of course, unclear but growing evidence of innate immune involvement in the disorder suggests that one reason the autoimmune issue has not been raised much may be because it is a kind of auto-immune disorder that researchers are only now beginning to recognize.

Conclusions

ME/CFS does, in several ways, look like an autoimmune disorder. Whether it comes to be considered one will depend on the results of more studies. With 80 auto-immune disorders identified and more under consideration, the auto-immune research field is an enormous one that receives more than a billion dollars in federal research funding a year. Getting even a part of CFS tied into could reap huge dividends for the disorder in terms of recognition and funding .

I’d be happy if it was classified and treated as one…as you say, that means respect, research money, and lots of viable treatments. Still, I have a really hard time thinking that pathogens may be at the heart of ALL autoimmune disorders somehow.

As a twenty-five year sufferer of CFS I can tell you the only way you will get any relief from this horrible illness is to start treating it like an autoimmune illness like lupus, which is what CFS is; an immune system in overdrive. Calm the immune system with medications that suppress the immune response and the symptoms of the illness will lessen. Exercise will only exacerbate the symptoms of CFS because exercise stimulates the immune response, which is exactly what you don’t want to do to a CFS sufferer.

I look at CFS as an autoimmune/neuroimmune disease. I try to explain to people that I am not sick in the conventional way that people think of illness. That my body is actually over-performing which can make you feel just as bad as one that is under-performing.

Is it an infection or a reaction? Is it is an infection that your body can’t defeat and you become weak and frail, or is your body over-reacting to everything; sending out an immune response that is too strong causing inflammation, irritable bowel, pain, flu-like symptoms etc.? A strong immune response can make you feel just as bad as a weak immune response; they are totally opposite problems, but produce the same symptoms. People who are experiencing an over-response of the immune system feel just as sick (eg autoimmune diseases, allergies/anaphylaxis), but don’t look as sick because their problem is not caused by a suppressed, poor-functioning immune system (eg cancer, diabetes etc), but one that is performing too well. In an ironic kind of way, people with CFS are actually too healthy.

Interesting that a strong and weak immune system can produce the same symptoms! What we do know is that the two major regulators of the immune response – the HPA axis and autonomic nervous system, appear to be perturbed in CFS – so its no real surprise that the immune response might be off.

The phenomenom called ‘sickness behavior’ which causes the flu-like symptoms that we have when we have a cold demonstrates the power of the immune system to cause strong symptoms. With an infection the idea is that the system causes alot of symptoms so that you rest and are not active (so you don’t spread the infection to others).

Cort: I came across this interesting article re: “sickness behavior” which left a lasting impression of the way i think about CFS – Quote from the article “For the first time it became clear,” says Dantzer. “Sickness behaviour is like fear–it is a state that makes the animal reorganise its priorities.” Just as the sight of a predator makes animals release hormones that drive the “flight-or-fight” response, infection triggers the release of cytokines, which make the animal rest and conserve its resources to fight the infection. And of course, sickness behaviour is not exclusive to rats–think of the last time you got flu.

Rachael, you write that a CFS patient should consider calming the immune system with medications that suppress the immune response. Would you mind me asking which medications you would suggest? Many thanks

Hi Annie: I take a number of things everyday. I have done a lot of experimenting in my lifetime and through trial and error, I have found what works best for me, that’s not to say it would work for someone else. Some of the things I take are foods and supplements that raise my dopamine levels in the morning (dopamine can act like a brake re: the immune system); over-the-counter pain medications (antiinflammatory) if needed in the afternoon (aspirin or ibuprofen) and sedating antihistamines at bedtime. I also take fish oil supplements in the a.m. I try to give my body things to slow it down a bit and replace what I feel it is depleted in. I always go back to that old saying about CFS, that it’s like ‘running-on-empty’. It’s certainly not perfect, but it seems to ease many of my CFS symptoms. This is certainly not medical advice and it may be of no benefit to anyone, but myself. Best wishes!

One day, it will be proven, that having a genetic predisposition, to develop an autoimmune illness and an environmental trigger is the cause of CFS. In some susceptible people that trigger may very well may be a virus, or infection. In others, some sort of stimulation, or change in the immune system (adverse vaccination reactions, a chemical poisoning, or a trauma eg surgery, accidents), something that causes the immune system to go haywire in genetically, predisposed individuals; those who were born with more sensitive immune systems than the average person.

Considering that I’ve had severe asthma from my early childhood until age 12… Have been suffering from eczema from age 17 to now (intermittently… Symptoms tend to flare up then remain dormant for some extended period of time)… That I may be investigated for eosinophilic esophagitis in the near future. And that, since I’ve been diagnosed with ME/CFS, we’ve managed to identify a miriad of new allergies (eggs!!! All types of pollen, dust mites…), and intolerances (soy, chocolate, avocados, cafeine…). On top of the allergies that we were already aware of (cats, some raw fruits, some raw nuts…). I’m thinking that my immune system was probably already pretty sensitive… And that the mononucleosis + other stress factors (including post-traumatic stress following a specific event) that all occurred within a 6 months period may indeed have made my immune system go completely haywire.

I imagine it autoimmune disorders will be caused by a complex mix; some will (do) have pathogen involvement and others will just represent an immune system with a new and damaging set point. Its a fascinating field of research that’s for sure.

I’ve been banging on and on about this for years now. It’s about time someone bothered to look at this..pity it wasn’t picked up on much much sooner! I personally think the changes in immune response in pregnancy are the driver for improvement. Both my pregnancies led to huge improvements after 20 weeks. BUT: I had no change in my ME related to my cycle (my ME dates back to age 10), two attempts at HRT to replicate the pregnancy improvement were non-beneficial ( the second with added testosterone was particularly troublesome), and natural progesterone supplementation also created adverse effects. I am ANA positive. I see no reason why ME being autoimmune (which I’ve presumed to be the case for many years now) and also being at the mercy of a pathogen at some point / contemporaneously should be mutually exclusive. I also have a history of Coxsackie B in my long experience of this illness.

So interesting Rosie! Your improvement during pregnancy but no improvement with the HRT does suggest that some other than hormones are involved and that would lead us, one would think, to the immune system and what happens there during pregnancy. The Peterson/Staines group is looking at the expression of genes involved in pregnancy in ME/CFS and preliminary results suggest they are finding something..perhaps that study will suggest which other part of your system is involved.

I do hope so One of the gynaecologists who oversaw my first attempt at HRT also suggested that had the sex hormones per se been the cause of the improvement then I should have seen almost immediate relapse at parturition. This was no the case. Indeed the course of improvement and the continued drag of feeling better for about 18 months post-birth rather mirrors the time scale of Fluge and Mella’s work…..which I think is possibly more than coincidence and worth more exploration.

I have had the opportunity to visit one of the premier CFS MD practioners in the country (she lives in Miami, hint, hint) and I made it clear that my symptoms were clearly pronounced from my earliest memories. I never had any single trauma, accident, illness as a trigger. Lo these many decades, there was never any doubt that CFS is an inherented gene, and probably an autoimmune condition. Both my mother and grandmother had constant CFS-related symptoms throughout their lives, but were written off as a fragile flowers, sensitive souls, you know how ladies are: given to “hysteria.” (Nice to know docs were still relying on Victorian diagnoses back in the 80s.) What they had was some form of CFS autoimmunity. Since I feel a little vindicated on this point, I would like to also forecast that CFS will be found to occur most likely in younger/youngest children of large families, or grandchildren (or sometimes great grandchildren) of large families. Families of 8 or 10 kids were quite common several generations ago. I have been to numerous “CFS support group” meetings and have seen a pattern; in addition to my own experience. Lastly, I do think that one means of dividing the CFS patient population into subgroups would be how they react to pain medication. Those who do get relief from hydro/oxycodone are probably doing so because their “oxidative stress” is being temporarily abated. Those might be the ones most likely to benefit from drugs like rituximab.There is probably a subset of patients who do have a virus or a bug of some sort causing their illness, and I suspect they will probably be unaffected by anti-autoimmune therapties.

“Why women are more prone to develop autoimmune disorders is not clear but researchers think it probably have to do with two factors; an increased inflammatory response and the involvement of sex hormone, both of which are subjects of interest in ME/CFS. (Interestingly, men with autoimmune disorders often have more severe forms of them.)”

This isn’t true of ME: it does seem to affect women in greater numbers, and with greater severity, than men. I have heard of just one long-term severe case in which a male was (by his mother’s definition) “completely isolated” (he was like that for 8yrs but then started to recover). Pretty much all the cases I’ve heard of in which someone was bedridden for a very long period (as in decades) or had extreme health complications involved a female sufferer. There may be some males that match this description, but they are a minority.

That may very well be true. I guess we would need a good survey to substantiate this. I’ve known of several males with really severe ME/CFS and of course many females as well. There may be trends that fit autoimmune disorders as a whole which do not fit particular disorders. (For instance in some autoimmune disorders women do not experience relief during pregnancy.)

Cort, This was a great, comprehensive review of the topic of autoimmunity as it may relate to ME/CFS!

I am spending this fall in Norway. The Retuximab study has, understandably gotten quite a bit of attention over here and I’m enclosing excerpts from a recently published article below:

Erling Ulvestad, MD, PhD, Professor in Immunology, and Chief of the Department of Micobiology at the Haukeland University Hospital in Bergen, Norway, commenting on the Rituximab-study (originating at his institution) – stated (as quoted in the Norwegian medical newspaper ‘Dagens Medisin’ – [Today’s Medicine] October 27, 2011, page 5. “): “ I really don’t know why one has to make such a distinction between psychological and somatic disease. Even in depressive disorders somatic mechanisms are central, as for example changes in the signaling mechanisms in the brain. We know that psychological stress will impact B-lymphocyte function.”
He continues, “ it is a grave mistake to isolate psychological from somatic disease.
- As an example, there is a natural explanation why the Lighting Process can give improvement in some ME-patients. By changing the way we think, – the way our brain function, we will also change the immune system. There is therefore no conflict between the theory that immunology have a central role in the illness of ME, and that different cognitive methods of therapy can have a positive effect on this illness”, professor Ulvestad underscores.

Professor Ulvestad has praise for the researchers behind the Rituximab study, and points out that the reults are providing a possible direction for further study, as this therapy is destroying a particular group of cells. When this provides improvement in the illness of ME, the implication is that the mechanism of the disease may be uncovered by further study in this direction. The results are trustworthy and very well documented. The researchers did solid immunological work”

Much more work has to be done, the work has to be replicated in other clinical settings. The illness of ME/CFS may have several sub-groups. It is likely that Retuximab only is effective in a sub-group. It would be very interesting to find out what triggered the illness in the sub-group that benefited from the Retuximab therapy. Was the trigger a viral infection, stress-related trauma, maybe a combination of the two, or something else?

The field of psychoneuroimmunology is an evolving one. I believe there is great potential benefit from an interdisciplinary approach to the study of the ME/CFS puzzle, and therefore hope the ME/CFS community can be open to this.

Agreed. Any emotion we human beings (and it is true for animals too) experience triggers a physiological response. And physiological abnormalities will make it harder for humans to effectively deal with emotions.

From a clinical point of view, insisting on dividing the two seems senseless. However, saying that ME/CFS is a psychiatric disorder and treating it only via psychotherapy or psychiatric drugs would be a mistake.

Knowing that people suffering from ME/CFS will experience an erratic physiological response to stress (a.k.a. changes requiring adaptation from mind and/or body), cognitive behavioral therapy (CBT), as well as other psychological approaches may be of great help in managing the symptoms.

I remember that my asthma attacks, and my eczema flare ups always became much worse when I was stressed out!

However, it doesn’t mean that asthma or eczema are psychiatric illnesses… Although, perhaps the trigger to the illness onset was an initial stress factor (or initial stress factors) that the body reacted to. Please note that the term “stress” includes viral infections, or even positive events like, say, a wedding. It truly is a synonym for: “any change that requires adaptation”.

Which came first… The hen or the egg? No matter what caused what, ME/CFS is a complex multisystemic syndrome that should be addressed as such. And, in my opinion, it implies caring for the mind, as well as the body as they both have a great influence of each other.

I often see ME/CFS as a major alteration in the internal mechanisms that are supposed to help maintain our homeostasis. Any internal or external changes, even a simple temperature variation, seems to be perceived as a threat.

Some people will develop Crohn’s disease, others multiple sclerosis… I developed ME/CFS. So while I’m taking care of my mind by doing CBT and learning relaxation techniques… I expect the medical community to look for ways to support my body and help it find its balance (its homeostasis), especially if we discover that ME/CFS is indeed an auto-immune disorder.

I love the connection to other disorders. For a while I’ve thought of CFS as one pathway and rhuematoid arthritis or multiple sclerosis as another. I suppose depression may even be another. As for mind/body stuff – I use a variety of techniques every day it definitely helps. My guess is that an erratic and overloaded autonomic nervous system just can’t handle stressors of any kind and negative thoughts are definitely a stressor – as is too much exercise, eating too much sugar, not getting enough sleep, etc. – each of which can floor me.

Stress is a well known trigger of asthma and my mother used stress reduction techniques for her auto-immune disorder 20 years ago. If the major stress response systems (HPA axis and ANS) are not working well in CFS – and they’re not – then it stands to reason that some of these techniques can be helpful. The fact that they are both major immune regulators suggests they would be a good idea to try.

Bravo to Drs. Malle and Fluge for pursuing doggedly with great determination why Rituximab works with some CFS sufferers and not others. In the course of their investigation, they will find out so much. It sounds like they are steadfast in their goals. If they can find out definitively if this is an autoimmune disease, and how B cells are involved, and why some people are helped and not others, and if there are subsets of the disease, this will be such a big step forward.
It will help to validate all of our assertions that this is a physical disease — and as someone who is about to have the 26th anniversary of having CFS, I’m adamant that this is the case.
I remember how sick I was with a flu before I got CFS, and that my spleen and liver were involved, and that I got some type of liver inflammation and symptoms related to that. And I was so sick those first few years that I wasn’t able to do anything.
And now that I can barely go out, have to pace everything, have had weeks where I can’t go outside, go have fun, go grocery shopping, go for a walk, do necessary errands, can’t make meals, can’t do laundry, etc.
I don’t know how anyone can figure out all of these techniques and steps to do. If I remember to take my vitamins and brush and floss my teeth and can read my newspaper (which sometimes I can’t do as I can’t lift my arms to hold it up) and pay my bills — on time — I consider it a good week.
I can’t wait to see what research comes up with, and I sure hope that other countries take this up like Norway is doing, thanks to this medical team. It should spur on more research and funding.
And meanwhile, Komaroff, the Lights, Natelson, Klimas, etc., continue their research. Komaroff says there are over 4,000 studies confirming physical biomarkers or objective confirmations of that.
I’m eager to see what develops. I’d like all this to happen quickly, as I’d like to have my life back, but I’ll wait [im]patiently.

I agree Kathy – if they can validate their finding again and figure out what’s going with those B-cells – its a huge, huge step for CFS. I’m feeling confident that future studies will be positive because the last one they did was so rigorous. The ideal situation would be for other researchers to quickly try to replicate. My guess is that there will be a big push to do that.

Yes, Cort. I agree with you on those critical B-cells, and whatever can be discovered about their link to CFS, and how they can be corraled into not malfunctioning.
I bet on Drs. Malle and Fluge to keep going, find out all they can, and that others will be spurred on by their dogged investigations.
Maybe we could suggest that they come here at some point and talk to — I don’t know — government agencies, like NIH, NCI, and doctors, researchers, etc.

As a possible epilogue to another fine research story by Cort, I have to report that Annette Whittemore is now suing Judy Mikovitz over alleged misappropriation of XMRV data and samples. Apparently, Mikovitz was fired by cell phone while in front of here home. Starting now scant funds that might be committed to cutting edge research (such as the topic of this article) will go into some lawyer’s pockets. The whole thing is now personal and ugly. Uggh. Let’s hope the Norwegians continue with their top-notch, professional, and thoroughly scientific research because I’m not sure many institutions have the will or the capability to do it in this country.

When they begin to understand, that we are not all immune-suppressed carbon copies of one another, they will be well on their way to finding a cure for CFS. Autoimmune illnesses are caused by an immune system in overdrive. Cancer, HIV and diabetes are more likely to develop in people with poor immune function. I have no more control over my illness (CFS), than a cancer patient does over his/her illness. Postitive thoughts, CBT and meditation may be beneficial for both conditions, but will cure neither illness.
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Psychiatrists have been very reluctant to accept the idea that depression (anxiety), which they know so well, may be caused by allergies to common environmental molecules such as foods, airborne particles, and chemicals. When patients were depressed and anxious, and at the same time suffered from diseases accepted as allergic, psychosomatic explanations (sickness behavior) were given (they just think they are sick; attention seekers; neurotic). This usually meant that a psychological explanation for the presence of the allergic reactions was invoked (in other words blame the patient). It couldn’t possibly be, that they were actually born with more sensitive immune systems and their complaints were real and not figments of their imaginations. Asthma for a long time was one considered of the seven major psychosomatic diseases.

The tricyclic antidepressants (eg amitriptyline) are third generation antihistamines. The discovery of the antihistamines was followed by their use as tranquilizers (they suppress histamine and thus the immune system). It’s peculiar that “low dose” amitriptyline helps many CFS sufferers because of their antihistaminic properties, not because they act upon the serotonin or sympathomimetic amine pathways. Tricyclic antidepressants are antidepressants largely because of their antihistaminic properties.

Interesting stuff Rachel. Yes – how about looking at the ‘body-mind’ connection as well? I think Dr. Unger at the last IACFS/ME conference mentioned how many so-called mood symptoms such as anxiety can be set off by things like low blood volume. This is a largely unexplored area it appears to me. I didn’t know that about asthma…Very interesting.

Also interesting Cort is your mention of low blood pressure and its involvement in anxiety. Many CFS patients not only suffer from flu-like symptoms, sleep disturbances, fatigue and pain/anxiety, but also have problems with their autonomic nervous system; problems with temperature regulation, heart rate (tachycardia) and many have low blood pressure including myself.

The neurotransmitter dopamine is an important regulator of blood pressure and an important neurotransmitter in the peripheral autonomic nervous system. The deficiency of dopamine/endorphins produces the syndrome of intense suffering known as withdrawal. Flu like symptoms; feelings of malaise; joint/muscle pain; problems regulating body temperature; low blood pressure; anxiety; agitation; insomnia; nausea; irritable bowel are signs and symptoms of both conditions.

CFS may be linked to dopamine/endorphin depletion (much like Parkinson’s Disease which may be an autoimmune illness) and an inability to restore sufficient levels of these neurotranmitters in the brain, anything that causes a further depletion (exercise, stress, aspartame, alcohol etc) will only make CFS symptoms worse (running on empty). That is why it is so important for people with CFS to pace themselves, or they will find themselves crashing (no dopamine/endorphins; no brake) and the immune system becomes hyper-responsive. Dopamine dysreguation is involved in many autoimmune conditions. These are just some of my thoughts about CFS because as a 25 year sufferer I have had a lot of time to think it.

A lot of time indeed :). That’s amazing – I had no idea that dopamine deficiency can cause those symptom. I believe, and I will have to check my notes, that Dr. Clauw believes that dopamine metabolism plays a key role in FM (and probably CFS – since he believes all these disorders are inter-related.)

When I heard about WPI suing Dr. Mikovits, the first thing I thought of was: This is really a big help to CFS sufferers — NOT! It’s a waste of time, money — a lot of it, resources, a researcher, and an institution which purports to help us. No good will come out of this for those who are ill.
It’s all self-serving, ego-driven and profit-driven.

This is not helping to get to the cause of CFS nor to find treatments that work. It does not advance science one iota.

It’s a fight about intellectual property rights, not about helping CFS-sufferers.

I always worry when science, research, disease and profit-making are mixed together.

I have hopes for the studies launched by Drs. Komaroff, Klimas, the Lights, etc.

However, I think that Drs. Malle and Fluge will go on doggedly to actually find scientific evidence for the autoimmune basis, the mysteries in the immune system, especially in B-cells. Hopefully, this will spur on more research and understanding here and elsewhere. They seem to have the drive and the resources to keep this up.

Maybe they should travel to the U.S. when their studies are more complete and discuss their findings with scientists, researchers, doctors, patients — and with the NIH, NCI, etc.

I forgot to say this regarding the post above mine. I have horrendous allergies, have had allergic shots, take antihistamines, use an asthma inhaler sometimes. I have to avoid tons of plants, flowers, plant-based shampoo (everything), herbs, etc. Every single thing that’s airborne makes it hard for me to breathe normally, as well as gives me headaches, vertigo, etc.
Amytriptylline has never stopped or lowered a histamine reaction — not ever, not once. It makes no difference on my terrible allergies.

Kathy, I became interested in amitriptyline because of it’s antihismanic effects. I can understand why it didn’t improve your allergies because it also raises serotonin levels in the brain. Serotonin has immune boosting effects that can actually worsen allergy symptoms. There is great variations in this illness and, of course, what works for one will not work for all. Amitriptyline isn’t one of my favorites either, but I have found other antihistamines with similar properties that are quite effective in relieving some of my symptoms.

It’s the antihismanic properties of amitriptyline that really interested me and why it was used for anxiety/depression. I just don’t think a lot of people know that the sedating effect tricyclic antidepressants have on the immune system (for some people) is due to its antihismanic properties, which I found interesting.
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The most potent antihistamine, doxepin hydrocholoride, was about 4 times more potent than amitriptyline hydrochloride, about 800 times more potent than diphenhydramine hydrochloride, and about 8,000 times more potent than desipramine hydrochloride.

I am actually in the Fluge/Mella Rituximab study at the moment, and have been since it started. I can confirm that it actually has a great effect on most of us. I have no doubt that ME/CFS is an autoimmune disorder. Fluge and Mella is really on to something here, and have been able to forsee exactly how my body would respond, while treating me as if I have an autoimmune disorder.
I think hope for a cure is in the near future, and maybe soon this treatment could be given to the rest of the CFS-sufferers. I consider myself to be extremely lucky to be a part of this =)

Given that the majority of people who suffer from ME/CFS have a history of being very active, which is known to have a detrimental effect on the immune system in itself, so there would seem to be the probability of the two being linked as a causative agent.

If CFS/ME is an autoimmune disorder, why does Isoprinosine help some patients get better? It should make them worse, shouldn’t it? I have been wondering for weeks and would be grateful for any smart thoughts!

For me my CFS/Me symptoms are sometimes exhaustion, but the worst part is the sore throat, the aching and generally feeling awful and fluish. Sometimes a bit of sickness too. It’s not that I feel ‘fatigued’, more generally ill.

One question I have is about infections. When I get a cold it takes me a while to recover, but afterwards I actually feel quite good. Almost like my immune system is satisfied it has fought the infection and then calms down for a bit from it’s hyper state. I wonder what the science behind that is?

All sections of the Phoenix Rising website are compiled by a layman. They are not a substitute for a physician and are for informational uses only. Please discuss any treatments in these pages with your physician.